Lecture 7.2

Question 1

The influence of ionization on drug absorption is important only in circumstances in which biologic
pHs vary dramatically, such as those in the stomach (varying from 1.5 to 7.0) and the urine (varying from 4.5 to 7.5).

True or false.

Answer 1

True

Question 2

Both ionized and nonionized drugs are absorbed from subcutaneous and intramuscular sites of injection,
ionization does not appear to play an important role in the passage of drugs across the capillary wall.

True or false

Answer 2

True

Question 3

Although drugs such as acetylsalicylic acid are best absorbed from an acidic medium such as that in stomach, most of the aspirin is absorbed in the upper small intestine. Why?

Answer 3

small intestine has a considerably greater absorptive surface

Question 4

Compare the total absorptive area of small intestine and the stomach.

Answer 4

small intestine and its microvilli:
200 m2

stomach:
1 m2

–>most drugs, whether nonionized or ionized and whether acidic, basic, or neutral, are absorbed mostly from the small intestine.

Question 5

Most drugs, whether nonionized or ionized and whether acidic, basic, or neutral, are absorbed mostly from the small intestine.

True or false.

Answer 5

True

Question 6

What is meant by perfusion rate in the context of drug absorption?

Answer 6

rate at which blood flows through the tissues surrounding the injection site

–> determines how quickly drug molecules can be carried away from injection site into the bloodstream

Question 7

State a scenario in which the perfusion rate has to be considered.

Answer 7

Morphine sulfate
–> morphine may not be absorbed in circulatory collapse and shock in which the peripheral circulation is impaired

–>for patient suffereing from injuries in accident, requires more morphine to induce analgeisc effect, lead to death when stabilised

Question 8

For drug that is administered through intramuscular and subcutaneous sites, how could the rate of absorption be increased and retarded?

Answer 8

increase: massaging the site of administration

decrease: place ice pack

Question 9

Name a method of deliberately retarding the absorption of drugs by reducing the peripheral absorption.

Answer 9

Local anesthetics combined with a vasoconstricting substance such
as epinephrine (adrenaline) & injected

• epinephrine prevent rapid absorption + enhance duration of action –> prevent systemic toxicity

Question 10

Name a vasoconstricting substance that could be combined with local anesthetics.

What is its purpose.

Answer 10

Epinephrine

prevent rapid absorption + enhance duration of action + prevent systemic toxicity

Question 11

For the factor concerning gastric emptying time, when should drugs be taken to allow rapid absorption?

Answer 11

on an empty stomach

Question 12

What kind of meals retard absorption?

Answer 12

meals with high fat content

Question 13

What class of drugs are anti-cholinergic drugs?

Answer 13

inhibit the action of acetylcholine, a neurotransmitter in the nervous system

Question 14

What are anti-cholinergic drugs used to treat?

Answer 14

• Overactive Bladder
• Management of Parkinson’s Disease
• Motion Sickness

Question 15

Name a anti-cholinergic drug

Answer 15

propantheline

Question 16

Should anti-cholinergic drugs be taken before or after meals? Why?

Answer 16

one hour before meals

Because anti-cholinergic drugs can inhibit secretion of gastric juice

Question 17

What are antacids for?

Answer 17

neutralize excess acid

Question 18

State how acid-peptic disease (APD) could be managed

Answer 18

anti-cholinergic drugs taken one hour before meals and antacids taken one hour after meals

Question 19

What is acid-peptic disease?

Answer 19

excessive production of acid in the stomach and damage to the stomach lining by pepsin and acid

Question 20

For the management of acid-pepsin disease (APD), anti-cholinergic drugs are taken one hour before meals and antacids taken one hour after meals. Why?

Answer 20

onset of action of anti-cholinergic drugs is between 1.5- 2 hrs

–> exert their peak effects at a time when the antacid remains in the stomach

Question 21

What are some possible reasons for inadequate plasma concentration of a drug following oral administration?

Answer 21

1. destroyed by acid hydrolysis
2. Forms insoluble complexes with polyvalent ions such as Ca2+
3. Not absorbed
4. first-pass effect

Question 22

Name 2 drugs that are destroyed by acid hydrolysis if orally administered.

Answer 22

penicillin G & erythromycin

Question 23

Name a class of drug that forms insoluble complexes with polyvalent ions such as Ca2+ if orally administered.

Answer 23

tetracyclines

Question 24

Name a drug that is not absorbed when it is orally administered

Answer 24

neomycin

Question 25

By far the most important reason for an inadequate plasma concentration following the oral or parenteral administration of a drug is the first-pass effect, which consists of the loss of a drug as it passes through the liver for the first time.

Answer 25

True

Question 26

How is drug transported from the small intestine to the liver?

Answer 26

through hepatic portal system after being absorbed into it by passive diffusion from small intestine

Question 27

What happens after it is metabolised by the liver?

Answer 27

enters systemic circulation or gall bladder--> bile--> small intestine

Question 28

Through what transport mechanism is the metabolised drug transported from the liver to the gall bladder?

Answer 28

carrier-mediated transport (active)

Question 29

What can happen to the drug in the small intestine?

Answer 29

absorbed, metabolised or excreted

Question 30

What is the drug 'nitroglycerin' for?

Answer 30

treating angina pectoris

Question 31

How is nitroglycerin administered?

Answer 31

sublingually

Question 32

Why is nitroglycerin administered sublingually?

Answer 32

- to bypass liver b/c in liver it can be inactivated --> inadequate conc - perfuses the coronary circulation more directly

Question 33

For nitroglycerin, apart from being taken sublingually to bypass the liver and to maintain adequate conc, how else could take first-pass effect be overcome? What problem is associated with it?

Answer 33

raising the dose but could create secondary problems such as hypertension

Question 34

The rate of distribution is the major determinant of the shape of the plasma concentration versus time curve following rapid intravenous administration. true or false

Answer 34

true

Question 35

The rate and extent of drug distribution from plasma are both highly variable between different drugs, and to a lesser degree, between individual patients. true or false

Answer 35

true

Question 36

Drugs interact with macromolecules in various body fluids and tissues, and this interaction influences both the pharmacokinetic and pharmacodynamic parameters. True or false.

Answer 36

True

Question 37

Are drugs distributed non-uniformly throughout the body?

Answer 37

Yes

Question 38

Whether given orally or parenterally, drugs are distributed non-uniformly throughout the body. Factors that regulate the drug distribution are:

Answer 38

◼ The lipophilic characteristics of the drugs ◼ The blood supply to the tissues ◼ The chemical composition of various organs and tissues

Question 39

The distribution of drugs not only influences their onset of action, but also at times determines their duration of action. State an example.

Answer 39

Thiopental (an intravenous anesthetic) --> onset in 10-20 secs bc rapid transport to brain --> duration of action 20-30mins because of subsequent redistribution to other tissues e.g. muscle and fat

Question 40

What are some plasma proteins?

Answer 40

Albumin (most abundant) prealbumin lipoproteins globulins

Question 41

What do site 1 and site 2 of albumin bind to?

Answer 41

Site 1: binds structurally unrelated substances Site 2: binds drugs in a selective manner

Question 42

Name drugs that bind to albumin at its site 1

Answer 42

warfarin, phenytoin, and sulfonamides

Question 43

Name drugs that bind to albumin at its site 2

Answer 43

diazepam , phenylbutazone, and ibuprofen

Question 44

What is the significance of plasma albumin?

Answer 44

exerts 80% of the colloid osmotic pressure of blood

Question 45

Apart from binding to albumin, what other proteins could drugs in plasma bind to?

Answer 45

 Alpha1-acid glycoprotein  Other glycoproteins such as corticosteroid-binding globulin and thyroxine-binding globulin  Lipoproteins

Question 46

Does drug bound to plasma protein exert any pharmacologic effect?

Answer 46

No

Question 47

What is the interaction between proteins and drug governed by?

Answer 47

the law of mass action, in that the proportion of bound drug remains constant, provided the binding sites are not saturated.

Question 48

What kind of interaction may exist between a drug and protein?

Answer 48

NOT A CHEMICAL RXN, but a reversible attachment -->half-life in order of ms ◼ Electrostatic ◼ London-Van der Waals ◼ Hydrogen binding ◼ Combinations of the above

Question 49

The response to a drug is determined by the unbound fraction present in the plasma. True or false

Answer 49

True. The concentration of unbound drug is often a better index of a drug's effective therapeutic level than the total drug

Question 50

What measurement does he clinical laboratory assessment of the plasma level of a drug in most cases involve?

Answer 50

measurement of bound-plus-unbound amounts of the agent

Question 51

The greater the amount of bound drug, the less rapidly will the plasma level of unbound drug ____________, as it is continuously being replenished through dissociation of the complex

Answer 51

decline

Question 52

The greater the amount of bound drug in plasma, ___________________________________.

Answer 52

the less rapidly will the plasma level of unbound drug decline

Question 53

Why is the binding of drug to plasma protein not usually a disadvantage?

Answer 53

less rapidly will the plasma level of unbound drug decline, as it is continuously being replenished through dissociation of the complex -->without binding = drug too transient

Question 54

Therapy is easier to control when a drug is stable in the body and its plasma concentration does not fluctuate widely. True or false

Answer 54

True

Question 55

Name a drug that does not become bound in plasma

Answer 55

heparin

Question 56

Name a drug that binds extensively (98%) to plasma proteins

Answer 56

phenylbutazone

Question 57

Toxic manifestations of drugs are frequent and considerably higher in individuals suffering from ___________________.

Answer 57

hypoalbuminemia (低血清蛋白) or altered plasma and tissue protein conc

Question 58

What happens when drug is administered after binding sites of plasma protein are saturated?

Answer 58

toxicity since excess drug remains free

Question 59

Can drugs alter the proteins binding of other agents? Give examples

Answer 59

Yes -Aspirin decreases the binding of thyroxine -binding of bilirubin hindered by many pharmacologic agents

Question 60

The more tightly bound drugs can displace the less firmly bound agents. True or false

Answer 60

true

Question 61

Give an example of a drug that covalently and irreversibly binds to an endogenous proteins and leads to sustained inhibition and toxicity

Answer 61

Isoflurophate binding to acetylcholinesterase

Question 62

What are the factors that affect the pharmacokinetics of a drug?

Question 63

What objectives does binding of drugs to plasma proteins and various subcellular components achieve?

Answer 63

1. drug does not disappear too rapidly from the locus of action 2. to allow sufficient amount of drug to reach locus of action to bring desired effect but not cause toxicity